ISSN (Print): 1574-8871
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Volume 16, 4 Issues, 2021
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ISSN (Print): 1574-8871
ISSN (Online): 1876-1038
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Cardiometabolic comorbidities in autoimmune rheumatic diseases: from pathogenesis to treatment
Reviews on Recent Clinical Trials, Volume 11, Number 3
Guest Editor(s): Francesco Ursini
Thank you very much for your support. I had a pleasant experience of submitting articles to BSP. BSP is a large scientific publication house playing its role in spreading knowledge worldwide. Its journals encompass a wide range of biomedical disciplines, especially pharmaceutical sciences. I can find a variety of journals suitable for my articles. I find many articles of BSP very interesting and educational.
Haemorrhoids are vascular cushions contributing approximately 15-20% of the resting anal pressure. There are three major
cushions, located in the left lateral, right anterior, and right posterior aspect of the anal canal, and occasionally minor cushions.
Haemorrhoidal Disease (HD) is defined as the symptomatic enlargement and distal displacement of the vascular cushions. It
is the commonest proctological disorder with an estimated prevalence rate which varies from 4.4%  to 39%  representing
an important medical, social but also economic problem.
In fact, millions of over-the-counter prescriptions and new drugs are discovered and put in the market every year . Furthermore,
patients often tend to use self-medication rather than an appropriate medical prescription, mostly because of the embarrassment
caused by the disease.
The precise etiopathogenesis of HD is still under debate but, nowadays, the theory of sliding anal canal lining [4, 5] is widely
accepted. However, recent studies have demonstrated the multifactorial nature of the disease by associating HD with a state
of inflammation with activation of the matrix metalloproteinases  or rather a family of proteolytic zinc-containing enzymes
which regulate extracellular proteins and tissue remodeling, that have been found to be increased in patients with HD.
The most common symptom is a painless bright red rectal bleeding, often requiring hospitalization and blood transfusions,
meanwhile anal pain is common in case of thrombosed external hemorrhoids . Other possible symptoms related to HD are
itching, fecal seepage, prolapse, and mucus discharge. Many of these complaints are frequent in different colorectal diseases,
such as anal fissure, rectal prolapse, inflammatory bowel disease (IBD), or colorectal neoplasms. For this reason, an appropriate
differential diagnosis, including colonoscopy , is mandatory.
HD is commonly graded using the classification described by Goligher  more than 30 years ago. Unfortunately, it has
several limitations because it does not consider the possible associated symptoms, the etiopathogenesis of the disease as well as
concomitant clinical situations. Consequently, some new scoring systems have been described and recently validated [10, 11].
Treatment for HD includes dietary and lifestyle modifications, medical treatment, office-based procedures, non-excisional
and excisional procedures.
The choice of the ideal treatment depends not only on the degree of the disease. In fact, the patient's will and lifestyle and
the surgeon's experience on certain techniques  should be considered.
Moreover, patients with particular clinical situations such as IBD, radiation proctitis, pregnancy, coagulopathies and immunosuppressive
disorders deserve more attention. In these special conditions, emerging technologies can probably play an important
Conservative treatment seems to be beneficial in all degrees of HD, especially in I and II degree . Office-based procedures
as sclerotherapy and rubber band ligation are the gold standard in case of symptomatic I–II and III-degree HD that fail
conservative treatment . Conversely, excisional haemorrhoidectomy, diathermic or with devices remains the treatment of
choice for the treatment of III and IV degree HD . However, recently, even in more advanced stages, the tendency to preserve
tissues and reduce post-operative pain through doppler-guided hemorrhoidal artery ligation and mucopexy is increasing
despite the higher recurrence rate.
Stapled haemorrhoidopexy is less used than some years ago, probably because of several life-threatening post-operative
complications  as well as for the increased use of very promising minimally-invasive techniques. Furthermore, the eTHoS
trial, one of the biggest multicentre and randomized trials demonstrated that stapled haemorrhoidopexy has a low possibility of
being cost-effective .
Post-operative complications after HD procedures, such as post-operative pain, anal stenosis or fecal incontinence, should
be considered because they may lead to extremely difficult situations . Consequently, proper pre-operative planning and
prompt post-operative identification are crucial to avoid long-term morbidity and mortality.
In the special issue, “Haemorrhoidal disease: From pathophysiology to surgical treatment” will be discussed concerning all
issues of HD.
The Emergency Medicine is a medical specialty that has been evolved rapidly in the last years, considering the increased
access of patients to the emergency room. This “evolution” requires a great basic cultural background and continuous updating.
For this reason, we have decided to publish a special issue with the idea to guide the daily activity of emergency physicians.
These “pills” are a concentrate of diagnostic and therapeutic interventions for the most common diseases faced in the
emergency setting. More than any other specialists, emergency physicians are constantly engaged in a sudden, unpredictable,
and sometimes critical relationship with the patient.
Our idea was to update on current knowledge and clinical practice, accordingly to the guidelines and evidence-based reports,
to provide the best management of the acute patients in the overcrowded and chaotic setting of emergency.
In this thematic issue, there exist 11 reviews.
The first review by Pennisi et al. deals with the management of respiratory failure with the modern ventilation techniques
that gained dignity of first line intervention for acute exacerbation of chronic obstructive pulmonary disease, assuring reduction
of the intubation rate, and rate of infection and mortality in the last ten years .
Another important contribution by Congedo et al. was on the treatment of pleural effusion in particular when and how to
drain. The paper illustrated the diagnostic steps by the principal radiological instruments, emphasizing the role of ultrasonography,
in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion
of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the
effusion and patient clinical conditions .
Zanza et al. focus their attention on the application of bedside ultrasound in clinical practice. In particular, on two types of
syndromes, no traumatic hypotension and dyspnea that can benefit a better diagnostic setting. Recent studies suggest that bedside
ultrasound is the best procedure for the evaluation of heart, lung, abdomen and deep vessels .
The interesting review on diabetic ketoacidosis by Pitocco et al. described some important goals of therapy, in particular,
how correct the dehydration and acidosis and how reverse ketosis restoring blood glucose concentration gradually to near
Another important chapter in emergency medicine is Sepsis, a life-threatening organ dysfunction, with high mortality rate.
During this disease are present a lot of alterations in different organs. One of those is the gastrointestinal tract with increased
permeability and bacterial translocation. This kind of intestinal alteration can be both cause and effect of sepsis. At the moment,
biological damage markers are aspecific, but the dosage of LPS, citrulline, lactulose/mannitol test, and fecal calprotectin
is becoming an excellent alternative with high specificity and sensitivity .
Siciliano et al. in their review article analyze the most important causes of infectious diarrhoea and their constellation of
signs and symptoms, providing an update on the diagnostic tools available in today’s practice and on the different treatment
options. Specific diagnostic investigations can be reserved for patients with severe dehydration, more severe illness, persistent
fever, bloody stools or immunosuppression. Since acute diarrhoea is most often self-limited and caused by viruses, routine
antibiotic use is not recommended for most adults with mild, and watery diarrhoea. However, when used appropriately, antibiotics
are effective against specific germs shigellosis, campylobacteriosis, C. difficile colitis, traveler ’s diarrhea, and protozoal
Ojetti et al. focused the attention on the burdened risk of life-threating haemorrhagic events, especially in elderly who take
new oral anticoagulants, nowadays widely used to prevent and treat thromboembolic events. The standard therapy with vitamin
K antagonist has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban,
edoxaban, dabigatran, betrixaban) showed better efficacy and safety compared to standard warfarin treatment and they
are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with
DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients
could benefit from the use of reversal agents. There are three reversal agents idarucizumab, andexanet alfa and ciraparantag,
the first two are utilized in the emergency setting in patients with an active major bleeding or who need urgent surgery .
On the field of gastrointestinal bleeding Riccioni et al. performed an interesting review on Rendu-Osler-Weber disease, a
rare inherited syndrome characterized by artero-venous malformations (AVMs or telangiectasia) with autosomal dominant
transmission. AVMs can occur in any organ of the body, most commonly in nose, pulmonary, hepatic, gastrointestinal and cerebral circulations. Patients have a high rate of complications related to bleeding, of them gastrointestinal bleeding accounts
for 10.8%. A combination of medical and endoscopic therapy is probably the best option .
Disk battery ingestion is a cause of access to the emergency department, especially in paediatric age. This problem, if not
well managed, may lead to serious injuries, with several complications involving the gastrointestinal and respiratory tract.
Petruzziello et al., in their review, analyze the literature of the last 25 years to make a decisional flow-chart that may help the
emergency physician .
Liver cirrhosis of any origin has always been a source of several emergencies for physicians working at the Emergency
Department. The most common emergencies are upper gastrointestinal bleeding, decompensated ascites and spontaneous bacterial
peritonitis, hepatic encephalopathy, and hepato-renal syndrome. Abenavoli et al. described their management both with
medical and interventional procedures .
Finally, a very hot topic is the management of immunotherapy adverse events in oncological patients with Anti-CTLA-4,
Anti-PD-1/PD-L1 monoclonal antibodies that become the standard-of-care in a growing number of indications. Brigida et al.
summarise different types of immunotherapy-related toxicities, together with their incidence and diagnosis, to simplify their
management, according to the different grade (from I to IV) .
We hope this collection of manuscripts will support the choice of the best-integrated, corrected diagnostic and therapeutic
approach, stimulating the ongoing research and providing indications for the future standardization of protocols in the emergency
We would like to thank all of the authors one more time for their excellent contributions, the Editors of "MEDICAL
EMERGENCIES" for this kind invitation to act as guest editors for this thematic issue and the valuable assistance by Editorial
Manager, Syed Faizan Akhtar in the processing and finalization of this special theme issue.
Refractory Angina (RA) is an increasingly-prevalent issue worldwide. With increasing age, the number of patients who
might not undergo conventional myocardial revascularization with Coronary Artery Bypass Grafting (CABG) or Percutaneous
Coronary Interventions (PCI) is increasing steadily. The exact number of such patients has been ignored; but it has been estimated
that, in Europe, there are about 75,000 new cases annually , while in the United States, the reported incidence stands
at roughly 50,000 new cases/year and prevalence from 600,000 to 1,800,000 overall . Due to limits in treatment, these patients
have been called “no-option” patients, their most common cause of unsuitability for CABG or PTCA being diffuse coronary
disease, either associated or not associated with small vessel disease. Comorbidities, excessively-old age, and the combination
of these two factors are further causes . Apart from second- and third-line anti-anginal medications - like Nicorandil,
ivabradine, ranazoline, trimetazidine, perhexiliine, allopurinol, molsidomine, and fasudyl/hydroxyfasudil - several nonpharmacological
methods have been developed over the last 20 years. These include laser trans-myocardial revascularization,
shockwaves, spinal cord stimulation, stellate ganglion block, pro-angiogenic gene therapy, lipoprotein apheresis, stem cells,
external counter-pulsation and, quite recently, coronary sinus reducer devices . Many of these techniques represent old ideas
and methods of revascularization, abandoned soon after the advent of cardiopulmonary bypass and coronary surgery, and resurrected
with modern technologies . Two further options existed in the past, both involving the potential of Internal Mammary
Arteries (IMAs) to develop collaterals; and both surgical. One dates back to Arthur Vineberg, a Canadian surgeon who developed
a technique to implant an IMA into an intra-myocardial tunnel . This allowed for neo-angiogenesis in the heart, next to
the site of the mammary artery implant, with the development of collaterals visible by coronary angiography. This technique,
after about 15 years of satisfactory results, was abandoned for some decades. Recently, a suggestion was made to resurrect it as
a way to address refractory angina .
Another old method involving the IMAs consisted of occluding them by ligature. This technique was invented by Davide
Fieschi, in 1939 , and reproduced by Cesare Battezzati [9, 10] and Robert Glover  in the fifties. The principle behind this
approach is that, if an IMA is ligated distal to its pericardiophrenic branch, blood flow might be redirected towards the heart
through a microvascular anastomotic network. This technique initially exhibited encouraging results, though conflicting opinions
existed [12, 13]. However, all discussions about this approach were abandoned, as well as Vineberg’s procedure, following
the advent of the heart-lung machine [14-16] and on-pump coronary surgery.
After 50 years of silence, since 2010, it has been proposed that ligating the IMA to develop collaterals, by occluding it distal
to the pericardiophrenic branch, could be adopted for patients with RA . By the same year, it was suggested that this could be
achieved surgically, with or without the help of Vascular Endothelial Growth Factors (VEGF), or alternatively by endovascular
occlusion [18, 19]. An experimental study on dogs published in 2012, which included both a surgical approach and the injection
of VEGF, though inconclusive due to the high mortality rate among the dogs, opened the way to rediscovering therapeutic IMA
occlusion . Subsequently, greater emphasis was placed upon IMA occlusion and, ultimately, a Swiss team adopted this
concept and has since published two papers, in 2014 and 2017, describing interesting results achieved in humans. In the first
study, they occluded the IMAs via balloon angioplasty, while simultaneously occluding the coronary vessels for a short period
of time . In the second study, they caused persistent occlusion of the right internal mammary artery for six weeks .
They disclosed that, in patients with IMA occlusion, there were improvements in the collateral flow index, fractional flow reserve,
ECG intracoronary ST segment, and anginal symptoms. This improvement occurred ipsilaterally, meaning that occluding
the left IMA generated improvements if the left anterior descending artery was involved; as well, occluding the right IMA resulted
in improvement if the right coronary artery was involved. Conversely, the circumflex coronary artery exhibited no benefit
from occlusion of both the right and left IMAs. The investigators concluded that IMA occlusion could increase extracardiac
ipsilateral coronary supply to the point of reducing ischemia in the dependent but not contralateral myocardial region. What is
remarkable is that these conclusions are practically identical to those reported by Italian authors in 1939 and 1955.
Despite these modern demonstrations, occluding IMAs for therapeutic purposes is only a slowly-advancing concept within
the scientific community. In a recent editorial, this field of discovery was called an “undiscovered country” , and the author
of the current editorial certainly agrees . The microvascular network that connects extra-cardiac vessels to the coronary
artery [25, 26], and the potential roles of IMA occlusion , remain almost ignored fields of research. As a result, in 2019 the
road towards therapeutic IMA occlusion for refractory angina , although re-opened after years being dormant, certainly
requires further studies and remains far from being an established therapeutic option.
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